BACKGROUND: The genetic signatures associated with the susceptibility to nontuberculous mycobacterial pulmonary disease (NTM-PD) are still unknown. In this study, we performed RNA sequencing to explore gene expression profiles and represent characteristic factor in NTM-PD.
METHODS: Peripheral blood samples were collected from patients with NTM-PD and healthy individuals (controls). Differentially expressed genes (DEGs) were identified by RNA sequencing and subjected to functional enrichment and immune cell deconvolution analyses.
RESULTS: We enrolled 48 participants, including 26 patients with NTM-PD (median age, 58.0 years; 84.6% female), and 22 healthy controls (median age, 58.5 years; 90.9% female). We identified 21 upregulated and 44 downregulated DEGs in the NTM-PD group compared to those in the control group. NTM infection did not have a significant impact on gene expression in the NTM-PD group compared to the control group, and there were no differences in the proportion of immune cells. However, through gene ontology (GO), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) analysis, we discovered that PARK2 is a key factor associated with NTM-PD. The PARK2 gene, which is linked to the ubiquitination pathway, was downregulated in the NTM-PD group (fold change, - 1.314, P = 0.047). The expression levels of PARK2 remained unaltered after favorable treatment outcomes, suggesting that the gene is associated with host susceptibility rather than with the outcomes of infection or inflammation. The area under the receiver operating characteristic curve for the PARK2 gene diagnosing NTM-PD was 0.813 (95% confidence interval, 0.694-0.932).
CONCLUSIONS: We identified the genetic signatures associated with NTM-PD in a cohort of Korean patients. The PARK2 gene presents as a potential susceptibility factor in NTM-PD .

BACKGROUND: The immunologic features of nontuberculous mycobacterial pulmonary disease (NTM-PD) are largely unclear. This study investigated the immunologic features of NTM-PD using digital spatial profiling techniques.
METHODS: Lung tissues obtained from six patients with NTM-PD between January 1, 2006, and December 31, 2020, at Seoul National University Hospital were subjected to RNA sequencing. Cores from the peribronchial areas were stained with CD3, CD68, and DNASyto13, and gene expression at the whole-transcriptome level was quantified using PCR amplification and Illumina sequencing. Lung tissues from six patients with bronchiectasis collected during the same period were used as controls. The RNA sequencing results were validated using immunohistochemistry (IHC) in another cohort (30 patients with NTM-PD and 15 patients with bronchiectasis).
RESULTS: NTM-PD exhibited distinct gene expression patterns in T cells and macrophages. Gene set enrichment analysis revealed that pathways related to antigen presentation and processing were upregulated in NTM-PD, particularly in macrophages. Macrophages were more prevalent and the expression of genes associated with the M1 phenotype (CD40 and CD80) was significantly elevated. Although macrophages were activated in the NTM-PD group T cell activity was unaltered. Notably, expression of the costimulatory molecule CD28 was decreased in NTM-PD. IHC analysis showed that T cells expressing Foxp3 or TIM-3, which facilitate the regulatory functions of T cells, were increased.
CONCLUSIONS: NTM-PD exhibits distinct immunologic signatures characterized by the activation of macrophages without T cell activation.

ANCA-associated vasculitides (AAV) comprise granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis. All forms may involve different organ systems, yet kidney and lung involvement are common and fatal in many cases. Here, we aimed to determine the predictive value of pulmonary disease manifestation and individual CT findings in AAV patients. Available CT scans and clinical information on mortality, renal outcomes, occurrence of relapses and damage scores were analysed retrospectively from a tertiary rheumatology center in Germany. We included a total of 94 AAV patients (49 with GPA, 41 with MPA). Forty-four patients had lung involvement with available CT scans, 70.5% of which with GPA and 72.7% with renal involvement. Nodule formation and cavities were more frequent among GPA patients, whereas ground-glass opacities (GGO), ILD and pleural effusion were observed predominantly in MPA patients. Over a median follow-up of 37 months, GPA patients had a slightly higher overall mortality, whereas end-stage kidney failure rates were significantly increased in MPA patients. Relapse frequencies were comparable between both entities. The presence of GGO and pleural effusion were associated with higher relapse rates, whereas nodules were negatively correlated with relapses. Notably, RTX-treated patients had less infections as compared to individuals under different therapies. Our data demonstrate the outstanding importance of characteristic CT patterns in AAV diagnosis assessment. Especially certain CT patterns including GGO and pleura effusion may help to identify patients who are at higher risk for relapsing disease.

With the advancement of tissue procurement techniques, in-depth knowledge of morphology is crucial for cytopathologists to diagnose neoplastic and nonneoplastic lung diseases optimally. Cytopathologists must also be well versed in immunohistochemistry/immunocytochemistry markers and their interpretation for an accurate diagnosis.

BACKGROUND: Pulmonary complications are common among children with sickle cell disease (SCD). However, there is little literature on associated lung function abnormalities in Uganda. We aimed to determine the prevalence, patterns, and factors associated with abnormal lung function among children with SCD in a tertiary care hospital in Uganda.
METHODS: A cross-sectional study was conducted among children aged 6 to 18 years at the SCD clinic (SCC) of Mulago National Super-Specialized Hospital between January 2020 and April 2021. Data on sociodemographic and clinical characteristics was collected using a standardized questionnaire. Laboratory investigations, including a complete blood count and serum lactate dehydrogenase (LDH), were done. Spirometry was performed following the ATS/ERS standards. Multivariable modified Poisson regression analysis was performed to determine factors associated with abnormal lung function.
RESULTS: A total of 332 participants were enrolled. The mean age was 11.7 ± 3.4 years, and 184 (55.4%) were female. Overall, 126 (37.9%) participants had abnormal lung function: 67/126 (53.2%) restrictive, 57/126 (45.2%) obstructive, and 2/126 (1.6%) mixed-ventilatory patterns. Factors associated with abnormal lung function were; serum LDH level > 600UL (aIRR: 1.89 95% CI: 1.2 - 7.4, p = 0.049), a history of acute chest syndrome (aIRR: 1.55, 95% CI: 1.06-2.25, p = 0.024), wasting (aIRR: 1.33, 95%CI: 1.02 - 1.72, p = 0.032), and use of charcoal for household cooking (aIRR: 1.49, 95% CI: 1.03-2.15, p = 0.035).
CONCLUSIONS: More than one-third of children with SCD in Uganda have lung function abnormalities. Strategies to improve nutrition, reduce exposure to charcoal smoke, and monitoring serum LDH levels may be important in preventing or managing abnormal lung function in this population. The identification of reversible and irreversible airway obstruction in children with sickle cell disease also highlights the need for targeted interventions to address these specific patterns of abnormal lung function.

BACKGROUND: This study compares the effect of positive end-expiratory pressure (PEEP) on postoperative pulmonary complications (PPCs) in patients with obesity undergoing laparoscopic bariatric surgery (LBS) under general anesthesia with mechanical ventilation.
METHODS: A comprehensive search was conducted in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Internet, Wanfang database, and Google Scholar for studies published up to July 29, 2023, without time or language restrictions. The search terms included \"PEEP,\" \"laparoscopic,\" and \"bariatric surgery.\" Randomized controlled trials comparing different levels of PEEP or PEEP with zero-PEEP (ZEEP) in patients with obesity undergoing LBS were included. The primary outcome was a composite of PPCs, and the secondary outcomes were intraoperative oxygenation, respiratory compliance, and mean arterial pressure (MAP). A fixed-effect or random-effect model was selected for meta-analysis based on the heterogeneity of the included studies.
RESULTS: Thirteen randomized controlled trials with a total of 708 participants were included for analysis. No statistically significant difference in PPCs was found between the PEEP and ZEEP groups (risk ratio = 0.27, 95% CI: 0.05-1.60; p = 0.15). However, high PEEP ≥ 10 cm H2O significantly decreased PPCs compared with low PEEP < 10 cm H2O (risk ratio = 0.20, 95% CI: 0.05-0.89; p = 0.03). The included studies showed no significant heterogeneity (I2 = 20% & 0%). Compared with ZEEP, PEEP significantly increased intraoperative oxygenation and respiratory compliance (WMD = 74.97 mm Hg, 95% CI: 41.74-108.21; p < 0.001 & WMD = 9.40 ml cm H2O- 1, 95% CI: 0.65-18.16; p = 0.04). High PEEP significantly improved intraoperative oxygenation and respiratory compliance during pneumoperitoneum compared with low PEEP (WMD = 66.81 mm Hg, 95% CI: 25.85-107.78; p = 0.001 & WMD = 8.03 ml cm H2O- 1, 95% CI: 4.70-11.36; p < 0.001). Importantly, PEEP did not impair hemodynamic status in LBS.
CONCLUSIONS: In patients with obesity undergoing LBS, high PEEP ≥ 10 cm H2O could decrease PPCs compared with low PEEP < 10 cm H2O, while there was a similar incidence of PPCs between PEEP (8-10 cm H2O) and the ZEEP group. The application of PEEP in ventilation strategies increased intraoperative oxygenation and respiratory compliance without affecting intraoperative MAP. A PEEP of at least 10 cm H2O is recommended to reduce PPCs in patients with obesity undergoing LBS.
BACKGROUND: CRD42023391178 in PROSPERO.

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Lung diseases affect pulmonary and respiratory function and are caused by bacterial viral and fungal infection as well as environmental factors. Unfortunately, symptom overlap between various pulmonary diseases often prevents clear differentiation and uncertain diagnosis. Accordingly, identification of specific markers of inflammatory activity in early disease stage could potential unveil the intrinsic molecular mechanisms of the underlying pathology. Proteomic studies aimed at understanding the genetic/environmental contributions to the development and progression of lung diseases represent a promising approach for diagnosis and treatment. The fluid phase of sputum represents a rich protein source and is frequently used in these studies. This chapter addresses causes of lung disorders, sputum composition, collection and processing as well as the clinical significance and challenges associated with the presence of interfering factors. Basics of proteomics and mass spectrometry are also described, together with the analytical approaches to investigate the sputum proteome. Finally, we explore the application of sputum proteomics in severe lung disorders including COVID-19 infection, chronic obstructive pulmonary disease, asthma, cystic fibrosis, lung cancer and tuberculosis.

This study aims to evaluate the role of TUSG in the postoperative period and the detection of early complications after surgical treatment, pulmonary resection, or decortication for infectious and inflammatory thoracic diseases, comparing with the standard method (Chest Radiography ‒ CXR).
Prospective non-randomized self-controlled study. Twenty-one patients over 16 years of age have undergone surgical treatment of inflammatory and infectious lung diseases. These patients were followed up with CXR and TUSG (performed on the 1st and 3rd postoperative days and/or after the chest tube removal).
Both exams demonstrated similar results regarding their ability to safely predict the adequate moment for chest drain removal. TUSG allowed chest drain removal in 30% of cases and CXR in 34%. Statistical analysis demonstrates that both exams have similar capabilities in detecting postoperative changes in the pleural space. However, the authors report that TUSG is statistically more accurate in detecting subcutaneous emphysema than CXR (p = 0.037, Kappa [κ = 0.3068]). The analysis of other parameters showed no statistical difference.
The authors conclude that TUSG in trained hands is equivalent to CXR in searching for postoperative complications regarding the surgical treatment of infectious and inflammatory thoracic diseases and can be used as a complement, and not a substitute, to CXR, when CCT is not feasible, or a more urgent diagnosis is needed.